The prevalence of Birt-Hogg-Dubé syndrome in spontaneous pneumothorax patients.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disease,
characterized by skin fibrofolliculomas, renal cancer, multiple lung cysts and
pneumothorax.
The BHD-Syndrome is caused by a mutation in the FLCN-gene, which is localised
on chromosome 17, and encodes for the protein folliculin.
In over 80 percent of the patients with clinical BHD syndrome, a pathogenic
FLCN mutation can be demonstrated. The clinical expression is variable:
patients may present with skin lesions, renal cancer or pneumothorax.
The skin signs consist of are 1-5 mm multiple white or skin-coloured papules,
in particular on the face, neck and torso. These fibrofolliculomas are benign
lesions originating from hair follicles. Treatment is cosmetic with laser
techniques .
The observed prevalence of renal cancer in BHD-patients has varied between 6
and 35%. Renal cancer in BHD is diagnosed at a relative young age and is often
multifocal and/ or bilateral. For early detection and treatment FLCN mutation
carriers are advised to undergo yearly renal ultrasound.
Lung cysts have been found in 80-90% of patients with BHD syndrome, more often
localised basally than in the apical regions. These lung cysts may cause
pneumothorax. In about 25% of FLCN mutation carriers pneumothorax before the
age of 50 has been observed. Recurrent pneumothorax is common.
.
Familial occurrence of pneumothorax is found in about 10% the patients with
spontaneous pneumothorax.
As stated above, the clinical expression of BHD is variable. BHD families with
*pneumothorax-only*have been observed without skin or renal lesions.
Based on recent studies, 15-25% of the familial pneumothorax is due to an
underlying FLCN mutation.

To assess the prevalence of BHD among patients with spontaneous sporadic and
familial pneumothorax.

In 2009 a retrospective study was performed wherein 523 patients were included
who, in the period 1990-2008 were treated for spontaneous pneumothorax at our
hospital. For the present study we selected patients aged 18 years or older.
Patients who died were excluded from evaluation. After exclusion the remaining
380 patients received a letter with questions about their medical history,
pneumothorax, smoking behaviour, medication, and familial incidence of
pneumothorax and other diseases.
Information was received from in total 94 patients. These patients consented to
participate in a follow-up study.

The patients who gave permission for the follow up study will receive:
- An Invitation letter for the follow up study
- An Information brochure with information on Birt-Hogg-Dubé syndrome
- A consent form for examination at the outpatient Clinical Genetics
The investigations will consist of the following components:
- personal and family history
- expert dermatological examination which may include a skin biopsy
- The subgroup patients with familial pneumothorax will undergo CT-thorax
(5mSv) and ultrasound & MRI of the kidneys.
- Two blood tubes will be taken for FLCN mutation analysis

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